International Journal of
Environmental Research
and Public Health
Article
Metabolic Syndrome and Serum Liver Enzymes in the
General Chinese Population
Shuang Chen, Xiaofan Guo, Shasha Yu, Ying Zhou, Zhao Li and Yingxian Sun *
Department of Cardiology, the First Affiliated Hospital of China Medical University, Shenyang 110000, China;
[email protected] (S.C.); [email protected] (X.G.); [email protected] (S.Y.);
[email protected] (Y.Z.); [email protected] (Z.L.)
* Correspondence: [email protected]; Tel.: +86-248-3282-688
Academic Editor: Paul B. Tchounwou
Received: 14 December 2015; Accepted: 4 February 2016; Published: 17 February 2016
Abstract: Background: The aim of this study was to evaluate the associations between alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) with metabolic syndrome (MetS)
in the general Chinese population. Methods: This study was a multicenter, cross-sectional study which
was conducted in rural areas of China from the 2012 to 2013 Northeast China Rural Cardiovascular
Health Study (NCRCHS), and 11,573 adults with complete data were included in our final analysis.
Elevated ALT and AST levels were defined as >40 U/L. Serum ALT and AST levels within the
reference range were divided into quartiles, and their associations with MetS were evaluated by
logistic regressions. Results: A total of 7.4% and 3.5% participants had elevated serum ALT and AST
levels, respectively. The prevalence of MetS was 37.3% in males and 45.8% in females. After adjusting
for potential confounders, we found ALT level elevation, even within the reference range, was
independently associated with MetS. The odds ratio (OR) values of MetS in the ALT quartiles 2–4
groups within the reference range were 1.113 (95% CI: 1.019–1.280), 1.375 (95% CI: 1.212–1.560), 1.878
(95% CI: 1.650–2.138) compared with the ALT quartile 1 group, and OR in the elevated ALT group was
3.020 (95% CI: 2.496–3.653). Positive relationship for MetS was also observed in elevated AST group
(OR: 1.689, 95% CI: 1.314–2.171), but within the reference range, the AST level was not associated with
MetS. Conclusions: Serum ALT level, even within the reference range, was significantly associated
with MetS. However, only elevated AST levels above 40 U/L was positively associated with MetS.
Within the reference range, we did not find a relationship between AST levels and MetS.
Keywords: alanine aminotransferase;
liver enzymes
aspartate aminotransferase;
metabolic syndrome;
1. Introduction
Metabolic syndrome (MetS) is a cluster of disorders, including abdominal obesity, elevated
blood pressure, elevated blood glucose, hypertriglyceridemia, and reduced high-density lipoprotein
cholesterol (HDL-C) [1]. MetS is recognized to be strongly associated with type 2 diabetes mellitus [2,3]
and cardiovascular diseases (CVD) [4,5]. As CVD is one of the major causes of death throughout the
world, it has been a public health issue for early detection and early countermeasures against MetS,
which can prevent the progression of CVD.
Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are the common
liver enzymes of liver function tests and well-known markers of liver damage [6]. Among the liver
enzymes, ALT is the most specific marker of liver function and is used as an indirect marker of liver
inflammation or injury, but AST is the less specific marker because it also exists in other tissues [7].
It is reported that elevated ALT is closely associated with liver fat accumulation [8] and is considered
Int. J. Environ. Res. Public Health 2016, 13, 223; doi:10.3390/ijerph13020223
www.mdpi.com/journal/ijerph
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as a marker of nonalcoholic fatty liver disease (NAFLD) [9]. Moreover, it has been suggested that
NAFLD is considered to be a hepatic consequence of MetS [10–14]. Data linking elevated ALT and
AST levels with MetS was presented in several cross-sectional studies [15–17]. Thus, elevated ALT and
AST might be risk factors for MetS. However, it has been suggested that ALT still remained within
the reference range in many uncomplicated obesity subjects, and normal ALT levels cannot rule out
the existence of liver disease [18–20]. Until now, scanty studies among the general population have
reported the relationship between ALT within the normal range and MetS [12]. Therefore, the ALT
and AST levels, including within the reference range, need to be reviewed fully in relation to MetS.
Accordingly, the present study aimed to investigate (1) associations between elevated ALT and AST
levels with morbidity of MetS in a large-scale Chinese population; and (2) the relationship between
normal liver enzyme levels and MetS in this representative population.
2. Materials and Methods
2.1. Study Population
We conducted a cross-sectional study from July 2012 to August 2013 in rural areas of Liaoning
Province, which is called the Northeast China Rural Cardiovascular Health Study (NCRCHS).
A representative sample aged ě35 years was selected to describe the prevalence, incidence, and
natural history of cardiovascular risk factors. The study adopted a multi-stage, stratified, random
cluster-sampling scheme. In the first stage of sampling, three counties (Zhangwu, Dawa, and Liaoyang
County) were randomly selected to represent the south, east, and north of Liaoning province. In the
second stage, one town was randomly selected from each county (a total of three towns). In the
third stage, 8–10 rural villages were randomly selected from each township. In total, 26 rural villages
were finally included. All eligible permanent residents aged ě35 years from each village were
selected for participation (a total of 14,016 participants). 11,956 individuals agreed and completed
this cross-sectional study and the response rate was 85.3%. Approval for the NCRCHS was obtained
from the Ethics Committee of China Medical University (Shenyang, China, ethical approval number:
AF-SDP-07-1, 0-01). All participants provided written informed consent and all procedures were
performed in accordance with ethical standards. If the participants were illiterate, their proxies wrote
the informed consents for them. In this study, we used data of baseline and only participants with
complete data were included, making a final sample size of 11,573 (5357 men and 6216 women).
2.2. Data Collection
Data were collected during a single clinic visit by cardiologists and trained nurses using a standard
questionnaire by face-to-face interviews. Before the survey was performed, we invited all eligible
investigators to attend the organized training. The training contents included the purpose of this
study, how to administer the questionnaire, the standard method of measurement, the importance of
standardization, and the study procedures. A strict test was evaluated after this training; only those
who scored perfectly on the test could become investigators. During data collection, our inspectors
had further instructions and support.
Data on demographic characteristics, lifestyle risk factors, and medical history, were obtained by
interview with a standardized questionnaire. The questionnaire was designed by statistical experts
and clinical specialists. There was a central steering committee with a subcommittee for quality control.
The project management office of Liaoning Province will randomly check 5% of the questionnaires, the
unqualified questionnaires will be re-investigated again, and if the investigator made the unqualified
questionnaire, we will cancel the qualification of this investigator and abandon all of his or her
questionnaires. Educational level was divided into primary school or below, middle school, and high
school or above. Smoking and alcohol status were assessed by two types of questions, “Have you
ever smoked at least one cigarette per day for over six months/Have you ever taken alcohol at least
twice a week for over a year?” and “Do you smoke/take alcohol now?” Respondents were defined
Int. J. Environ. Res. Public Health 2016, 13, 223
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as current smokers/drinkers (those who answered YES to both questions), former smokers/drinkers
(those who answered YES to the first question and NO to the second one), and never smokers/drinkers
(those who answered NO to both questions). Physical activity included occupational and leisure-time
physical activity. Occupational and leisure-time physical activity were merged and regrouped into
the following three categories: (1) low—subjects who reported light levels of both occupational and
leisure-time physical activity; (2) moderate—subjects who reported moderate or high levels of either
occupational or leisure-time physical activity; and (3) high—subjects who reported a moderate or high
level of both occupational and leisure-time physical activity. Family income was classified as ď5000,
5000–20,000, and >20,000 CNY/year.
2.3. Blood Pressure Measurements
According to American Heart Association protocol, blood pressure was measured three times
in a sitting position at 2 min intervals after at least 5 min of rest in a quiet room with the use of
an automatic electronic sphygmomanometer (HEM-741C; Omron, Tokyo, Japan). Two doctors checked
the calibration of the Omron device using a standard mercury sphygmomanometer every month under
the British Hypertension Society protocol [21]. The mean of three BP measurements was taken and
used in all analyses.
2.4. Anthropometric Measurements
Waist circumference (WC) was measured at the minimum circumference between iliac crest and
the rib cage in the standing position at the end of normal expiration using a non-elastic tape. The body
mass index (BMI) was calculated using the formula weight (kg)/height2 (m2 ).
2.5. Biochemical Measurements
Fasting (12 h overnight) blood samples were collected by venepuncture in EDTA tubes.
Plasma was subsequently separated and frozen at ´20 ˝ C within 1 h for testing at a central, certified
laboratory after collection. Fasting plasma glucose (FPG), plasma total cholesterol (TC), triglycerides
(TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C),
serum ALT, AST, and other biochemical parameters were analyzed enzymatically on an Olympus
AU640 auto analyzer (Olympus, Kobe, Japan). All laboratory equipment was calibrated and blinded
duplicate samples were used.
2.6. Elevated Liver Enzymes Definition
Elevated serum ALT or AST level was defined as greater than 40 U/L.
2.7. Metabolic Syndrome Criteria
Metabolic syndrome was determined according to the unified criteria published in 2009 [22].
Abdominal obesity was defined as elevated WC: ě85 cm (male), ě80 cm (female). Elevated TG:
ě150 mg/dL (1.7 mmol/L). Reduced HDL-C: <40 mg/dL or 1.0 mmol/L (male), <50 mg/dL or
1.3 mmol/L (female). SBP ě130 mmHg, DBP ě85 mmHg, or taking antihypertensive agents, were
defined as hypertension. FPG of 5.6 mmol/L or higher or taking antidiabetic agents were defined
as hyperglycemia.
2.8. Statistical Analysis
Continuous variables were expressed as mean values and standard deviation (SD), whereas
categorical variables were described as frequencies and percentages. Since data were normally
distributed, continuous variables were compared between normal ALT and elevated ALT group
by using analysis of variance (ANOVA) test. χ2 -test analyses were used to examine associations
between the categorical variables. Quartiles of ALT and AST were created. Logistic regression was
Int. J. Environ. Res. Public Health 2016, 13, 223
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used to estimate the odds ratios (ORs) and 95% CIs for MetS after adjustment for age, race, BMI, and
lifestyle factors (smoking, drinking, family income, education, and physical activity). Serum ALT and
AST levels within the reference range were divided into quartiles so that the numbers of subjects in the
four categories were almost equal, and the lowest category was set as reference. A Pearson’s correlation
analysis was used to evaluate independent associations between liver enzyme levels and components
of Mets. The thresholds for liver enzyme levels were generated by ROC analysis. All statistical analyses
were performed using SPSS version 19.0 software (SPSS Inc., Chicago, IL, USA), and p < 0.05 indicated
statistical significance.
3. Results
Comparisons of characteristics between subjects with and without MetS were shown in Table 1.
A total of 11,573 adults (5357 men and 6216 women) aged ě35 years were included in the study.
The prevalence of MetS was 41.9% in general population (37.3% for men and 45.8% for women,
separately). Subjects with MetS had statistically significant higher values of SBP, DBP, WC, BMI, TC,
TG, LDL-C, FPG, but lower value of HDL-C compared to subjects without MetS (p < 0.001). As shown
in Figure 1, participants with elevated ALT or AST had statistically significant higher prevalence of
MetS compared to the participants with normal liver enzyme levels (p < 0.001).
Table 1. Baseline characteristics in subjects with and without metabolic syndrome (n = 11,573).
Mets
Non-Mets
(n = 4849)
(n = 6724)
Age, year
Male, %
Race (Han), %
Current smoking status, %
Current drinking status, %
55.5 ˘ 10.2
2003 (41.3)
4616 (95.2)
1508 (31.1)
975 (20.1)
52.7 ˘ 10.6
3355 (49.9)
6361 (94.6)
2589 (38.5)
1647 (24.5)
Education, %
Primary school or below
Middle school
High school or above
2643 (54.5)
1750 (36.1)
456 (9.4)
3127 (46.5)
2965 (44.1)
632 (9.4)
Physical activity, %
Low
Moderate
High
1673 (34.5)
2871 (59.2)
305 (6.3)
1768 (26.3)
4606 (68.5)
350 (5.2)
Family income, CNY/year, %
ď5000
5000–20,000
>20,000
635 (13.1)
2619 (54.0)
1595 (32.9)
807 (12.0)
3685 (54.8)
2232 (33.2)
History of CVD, %
SBP, mm Hg
DBP, mm Hg
WC, cm
BMI, kg/m2
TC, mmol/L
TG, mmol/L
HDL-C, mmol/L
LDL-C, mmol/L
FPG, mmol/L
ALT, U/L
AST, U/L
946 (19.5)
150.6 ˘ 22.6
86.1 ˘ 11.6
88.5 ˘ 8.3
26.8 ˘ 3.4
5.5 ˘ 1.2
2.3 ˘ 1.9
1.2 ˘ 0.3
3.1 ˘ 0.9
6.5 ˘ 2.1
25.3 ˘ 18.0
22.6 ˘ 11.7
800 (11.9)
135.6 ˘ 22.0
79.2 ˘ 11.0
78.1 ˘ 8.4
23.4 ˘ 3.2
5.1 ˘ 1.0
1.1 ˘ 0.8
1.5 ˘ 0.4
2.9 ˘ 0.8
5.5 ˘ 1.0
20.4 ˘ 18.5
21.8 ˘ 12.2
Variables
p-Value
Total
(n = 11,573)
<0.001 *
<0.001 *
0.136
<0.001 *
<0.001 *
53.8 ˘ 10.6
5357 (46.3)
10,968 (94.8)
4086 (35.3)
2617 (22.6)
<0.001 *
5763 (49.8)
4717 (40.8)
1093 (9.4)
<0.001 *
3441 (29.7)
7479 (64.7)
653 (5.6)
0.249
1441 (12.5)
6306 (54.5)
3826 (33.0)
<0.001 *
<0.001 *
<0.001 *
<0.001 *
<0.001 *
<0.001 *
<0.001 *
<0.001 *
<0.001 *
<0.001 *
<0.001 *
0.001 #
1712 (15.1)
141.8 ˘ 23.5
82.1 ˘ 11.8
82.4 ˘ 9.8
24.8 ˘ 3.7
5.2 ˘ 1.1
1.6 ˘ 1.5
1.4 ˘ 0.4
2.9 ˘ 0.8
5.9 ˘ 1.6
22.5 ˘ 18.4
22.1 ˘ 12.0
Notes: Data are expressed as the mean ˘ SD or as n (%). Abbreviations: CNY, China Yuan (1 CNY =
0.161 USD); CVD, cardiovascular disease; SBP, systolic blood pressure; DBP, diastolic blood pressure; WC,
waist circumference; BMI, body mass index; TC, total cholesterol; TG, triacylglycerol; HDL-C, high-density
lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; FPG, fasting plasma glucose; ALT, alanine
aminotransferase; AST, aspartate aminotransferase. * p < 0.001, # p < 0.05.
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Figure 1. Comparison of the prevalence of metabolic syndrom in both groups of ALT/AST < 40 U/L
Figure
1. Comparison of the prevalence of metabolic syndrom in both groups of ALT/AST ď 40 U/L
and ALT/AST > 40 U/L.
and ALT/AST > 40 U/L.
Tables 2 and 3 showed characteristics of participants stratified by ALT and AST quartiles,
Tables
2 andThe
3 showed
characteristics
of participants
stratified
by for
ALT
and AST
quartiles,
respectively.
study population
was divided
into five groups:
one group
elevated
ALT/AST
(>40 U/L),
andstudy
four groups
withinwas
reference
range
according
to ALT/AST
quartile.
The serumALT/AST
ALT
respectively.
The
population
divided
into
five groups:
one group
for elevated
and AST
quartile
as follows:
U/L, 14.0–17.6
17.6–23.0
23.0–40 U/L
for ALT;
<17.0
U/L, ALT
(>40 U/L),
and
four was
groups
within<14.0
reference
range U/L,
according
toU/L,
ALT/AST
quartile.
The
serum
17.0–20.0
U/L,
20.0–23.0
U/L,
23.0–40
U/L
for
AST.
Subjects
in
the
highest
ALT
or
AST
group
were
and AST quartile was as follows: <14.0 U/L, 14.0–17.6 U/L, 17.6–23.0 U/L, 23.0–40 U/L for ALT;
more likely to be men, current smokers and drinkers, had higher blood pressure, WC and BMI, had
<17.0 U/L, 17.0–20.0 U/L, 20.0–23.0 U/L, 23.0–40 U/L for AST. Subjects in the highest ALT or AST
higher TC, TG, LDL-C, FPG, and higher prevalence of MetS, but had lower HDL-C level than those
group were more likely to be men, current smokers and drinkers, had higher blood pressure, WC and
of subjects in the lowest ALT or AST quartile group.
BMI, had higher TC, TG, LDL-C, FPG, and higher prevalence of MetS, but had lower HDL-C level
than those of subjects
in2.the
lowest ALT
ASTaccording
quartile to
group.
Table
Characteristics
of or
subjects
the ALT quartiles (n = 11,573).
Normal ALT
Variables
Elevated ALT
Table
2. Characteristics of
subjects
according
the ALT
Quartile
1
Quartile 2 to Quartile
3 quartiles
Quartile 4(n = 11,573).
Metabolic syndrome, %
ALT, U/L
Variables Age, year
Male, %
Quartile 1
Race (Han), %
smoking
Metabolic Current
syndrome,
% status, %979 (30.9)
Current
ALT,
U/L drinking status, %11.4 ˘ 2.2
Age,High
yearschool or above, %54.8 ˘ 11.9
High Physical activity, %
Male,
%
1028 (32.2)
Family income >20,000 CNY/year, %
Race (Han),
%
3056 (95.8)
History of CVD, %
Current smoking SBP,
status,
%
1026 (32.2)
mmHg
Current drinkingDBP,
status,
%
497 (15.6)
mmHg
WC, cm
High school or above,
%
280 (8.8)
BMI, kg/m
High Physical activity,
%2
177 (5.5)
TC, mmol/L
Family income >20,000
1057 (33.1)
TG, mmol/L
CNY/year,
%
HDL-C, mmol/L
History of CVD,
%mmol/L 474 (15.2)
LDL-C,
SBP, mmHg
138.5 ˘ 23.9
FPG, mmol/L
979 (30.9)
780 (36.1)
1149 (42.5)
1376 (52.4)
11.4 ± 2.2
15.9 ± 0.9
20.2 ± 1.7
29.5 ± 4.7
54.8 ± 11.9 Normal
54.3 ± ALT
10.8
54.1 ± 9.8
52.9 ± 9.5
1028Quartile
(32.2)
13483 (49.6) Quartile
1554 (58.9)
2 864 (39.9)
Quartile
4
3056 (95.8)
2049 (94.5)
2551 (93.9)
2492 (94.5)
1026 (32.2)
994 (36.6) 1376
1005
(38.1)
780 (36.1) 732 (33.8)
1149 (42.5)
(52.4)
497 (15.6)
15.9 ˘ 0.9 423 (19.5)
20.2 ˘ 681
1.7 (25.1) 29.5732
˘(27.7)
4.7
28054.3
(8.8) ˘ 10.8 180 (8.3)
257 (9.5) 52.9280
54.1 ˘ 9.8
˘(10.6)
9.5
177 (5.5)
142 (5.2)
(6.1)
864 (39.9) 128 (5.9)
1348 (49.6)
1554162
(58.9)
1057 (33.1)
662 (30.5)
893 (32.9)
870 (33.0)
2049
(94.5)
2551
(93.9)
2492
(94.5)
474 (15.2)
320 (15.1)
398 (14.9)
410 (15.8)
994 (36.6)
(38.1)
138.5 732
± 23.9(33.8)141.6 ± 23.8
142.7 ± 23.6 1005
143.9
± 22.5
681 (25.1)
(27.7)
79.7 ±423
11.5(19.5) 81.2 ± 11.8
82.3 ± 11.6 73284.0
± 11.6
78.7 ±180
8.9 (8.3) 80.9 ± 9.0
83.1 ± 9.5 28085.8
± 9.7
257 (9.5)
(10.6)
23.5 ±128
3.2 (5.9) 24.4 ± 3.5
25.0 ± 3.5 16225.9
± 3.7
142 (5.2)
(6.1)
5.1 ± 1.0
5.1 ± 1.1
5.3 ± 1.1
5.4 ± 1.1
893 (32.9)
(33.0)
1.3 ±662
1.0 (30.5) 1.4 ± 1.1
1.6 ± 1.4 870 2.0
± 1.8
1.4 ± 0.4
1.4 ± 0.4
1.4 ± 0.4
1.4 ± 0.4
398 (14.9)
(15.8)
2.8 ±320
0.8 (15.1) 2.9 ± 0.8
2.9 ± 0.8 410 3.0
± 0.9
˘ 23.6
˘±22.5
5.7141.6
± 1.5 ˘ 23.85.8 ± 142.7
1.7
5.9 ± 1.5 143.96.1
1.6
536 (62.6)
65.6 ± 43.4
51.0 ± 9.4 ALT
Elevated
563 (65.5)
820 (95.3)
329
536(38.3)
(62.6)
284 (33.0)
65.6
˘ 43.4
96 (11.2)
51.0
˘ 9.4
44 (5.1)
563
(65.5)
344 (40.0)
820 (95.3)
110 (13.1)
329±(38.3)
144.8
22.1
284± (33.0)
85.9
12.0
88.0
10.1
96 ±(11.2)
26.7
4.2
44±(5.1)
5.5 ± 1.3
344
2.3 ± (40.0)
2.1
1.3 ± 0.4
110
3.1 ± (13.1)
0.9
144.8
˘ 22.1
6.1 ± 1.8
p-Value
<0.001 *
<0.001 *
<0.001
*
p-Value
<0.001 *
0.020 #
<0.001
*
<0.001
*
<0.001
*
<0.001
*
<0.001
*
<0.001
*
<0.001 *
<0.001 *
<0.001 *
0.020 #
0.440
<0.001
*
<0.001
*
<0.001
*
<0.001
*
<0.001
*
<0.001
*
<0.001
*
<0.001
*
<0.001 *
<0.001
*
<0.001
*
<0.001 *
<0.0010.440
*
<0.001
*
<0.001
*
DBP,
mmHg
˘ 11.5
11.8
˘ 11.6
84.0
˘expressed
11.6
85.9
12.0 ± SD <0.001 *
Notes:
The between cut79.7
points
are 14.0, 81.2
17.6, ˘
and
23.0 for82.3
normal
ALT. Data
are
as
the˘mean
WC, cm
78.7 ˘ 8.9
80.9 ˘ 9.0
83.1 ˘ 9.5
85.8 ˘ 9.7
88.0 ˘ 10.1
<0.001 *
or as n (%). Abbreviations: ALT, alanine aminotransferase; CNY, China Yuan (1 CNY = 0.161 USD);
23.5 ˘ 3.2
24.4 ˘ 3.5
25.0 ˘ 3.5
25.9 ˘ 3.7
26.7 ˘ 4.2
<0.001 *
BMI, kg/m2
cardiovascular disease;
TC,CVD,
mmol/L
5.1 ˘ 1.0SBP, systolic
5.1 ˘blood
1.1 pressure;
5.3 ˘ DBP,
1.1 diastolic
5.4 ˘blood
1.1 pressure;
5.5 ˘WC,
1.3 waist <0.001 *
BMI, body
TC,˘ total
TG, triacylglycerol;
TG,circumference;
mmol/L
1.3 ˘mass
1.0 index;1.4
1.1 cholesterol;
1.6 ˘ 1.4
2.0 ˘ 1.8 HDL-C,
2.3high-density
˘ 2.1
<0.001 *
HDL-C,
mmol/L
1.4 ˘ 0.4low-density
1.4 ˘
0.4
1.4 ˘ 0.4 FPG, fasting
1.4 ˘ 0.4
1.3 ˘ *0.4
lipoprotein
cholesterol; LDL-C,
lipoprotein
cholesterol;
plasma glucose.
p < 0.001, <0.001 *
LDL-C,
2.8 ˘ 0.8
2.9 ˘ 0.8
2.9 ˘ 0.8
3.0 ˘ 0.9
3.1 ˘ 0.9
<0.001 *
# p <mmol/L
0.05.
FPG, mmol/L
5.7 ˘ 1.5
5.8 ˘ 1.7
5.9 ˘ 1.5
6.1 ˘ 1.6
6.1 ˘ 1.8
<0.001 *
Notes: The between cut points are 14.0, 17.6, and 23.0 for normal ALT. Data are expressed as the mean ˘ SD
or as n (%). Abbreviations: ALT, alanine aminotransferase; CNY, China Yuan (1 CNY = 0.161 USD); CVD,
cardiovascular disease; SBP, systolic blood pressure; DBP, diastolic blood pressure; WC, waist circumference;
BMI, body mass index; TC, total cholesterol; TG, triacylglycerol; HDL-C, high-density lipoprotein cholesterol;
LDL-C, low-density lipoprotein cholesterol; FPG, fasting plasma glucose. * p < 0.001, # p < 0.05.
Int. J. Environ. Res. Public Health 2016, 13, 223
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Table 3. Characteristics of subjects according to the AST quartiles (n = 11,573).
Normal AST
Variables
Metabolic syndrome, %
AST, U/L
Age, year
Male, %
Race (Han), %
Current smoking status, %
Current drinking status, %
High school or above, %
High Physical activity, %
Family income>20,000
CNY/year, %
History of CVD, %
SBP, mm Hg
DBP, mm Hg
WC, cm
BMI, kg/m2
TC, mmol/L
TG, mmol/L
HDL-C, mmol/L
LDL-C, mmol/L
FPG, mmol/L
Elevated AST
p-Value
1229 (44.9)
28.0 ˘ 4.0
54.6 ˘ 10.3
1642 (59.6)
2572 (93.4)
1060 (38.5)
926 (33.6)
264 (9.6)
146 (5.3)
209 (51.5)
64.6 ˘ 37.6
52.4 ˘ 10.0
283 (69.5)
375 (92.1)
195 (47.9)
186 (45.7)
38 (9.3)
16 (3.9)
<0.001 *
<0.001 *
<0.001 *
<0.001 *
<0.001 *
<0.001 *
<0.001 *
0.094
0.001 #
664 (30.8)
820 (29.8)
134 (32.9)
<0.001 *
312 (14.8)
144.1 ˘ 23.9
82.5 ˘ 11.7
82.5 ˘ 10.1
24.7 ˘ 3.6
5.3 ˘ 1.1
1.6 ˘ 1.4
1.4 ˘ 0.4
3.0 ˘ 0.8
5.8 ˘ 1.4
410 (15.2)
146.6 ˘ 22.7
83.9 ˘ 11.9
84.1 ˘ 10.2
25.3 ˘ 3.8
5.4 ˘ 1.1
1.8 ˘ 1.7
1.5 ˘ 0.4
2.9 ˘ 1.0
5.8 ˘ 1.3
45 (11.4)
146.4 ˘ 23.8
86.2 ˘ 12.4
84.9 ˘ 10.4
25.3 ˘ 4.6
5.4 ˘ 1.5
2.3 ˘ 2.1
1.3 ˘ 0.3
3.0 ˘ 0.9
6.2 ˘ 1.9
0.103
<0.001 *
<0.001 *
<0.001 *
<0.001 *
<0.001 *
<0.001 *
<0.001 *
<0.001 *
<0.001 *
Quartile 1
Quartile 2
Quartile 3
Quartile 4
1384 (41.5)
15.2 ˘ 1.7
52.2 ˘ 10.7
1157 (34.4)
3232 (96.2)
1059 (31.5)
449 (13.4)
326 (9.7)
199 (5.9)
1150 (39.8)
18.9 ˘ 0.8
54.3 ˘ 10.7
1218 (42.0)
2764 (95.3)
999 (34.5)
565 (19.5)
260 (9.0)
156 (5.4)
848 (39.6)
21.8 ˘ 0.9
55.0 ˘ 10.4
1057 (49.1)
2025 (94.0)
773 (35.9)
491 (22.8)
205 (9.5)
136 (6.3)
1250 (37.2)
958 (33.0)
484 (14.7)
136.7 ˘ 22.2
80.3 ˘ 11.4
81.3 ˘ 9.4
24.5 ˘ 3.4
5.1 ˘ 1.0
1.5 ˘ 1.2
1.6 ˘ 0.6
2.8 ˘ 0.8
6.1 ˘ 2.1
461 (16.2)
140.7 ˘ 23.0
81.4 ˘ 11.6
81.7 ˘ 9.4
24.6 ˘ 3.7
5.2 ˘ 1.0
1.5 ˘ 1.2
1.4 ˘ 0.3
2.9 ˘ 0.8
5.8 ˘ 1.4
Notes: The between cut points are 17.0, 20.0, and 23.0 for normal AST. Data are expressed as the mean ˘ SD
or as n (%). Abbreviations: AST, aspartate aminotransferase; CNY, China Yuan (1 CNY = 0.161 USD); CVD,
cardiovascular disease; SBP, systolic blood pressure; DBP, diastolic blood pressure; WC, waist circumference;
BMI, body mass index; TC, total cholesterol; TG, triacylglycerol; HDL-C, high-density lipoprotein cholesterol;
LDL-C, low-density lipoprotein cholesterol; FPG, fasting plasma glucose. * p < 0.001, # p < 0.05.
Table 4 and Figure 2 presented the multiple logistic regression analysis for MetS. The adjusted
odds ratios for having MetS, for ALT and AST separately, in the five groups, were depicted in Figure 2.
After adjustment for age, sex, race, smoking status, alcohol intake, education degree, physical activity,
family income, BMI, and history of CVD, we found that both elevated ALT and elevated AST were
associated with higher prevalence of MetS (OR 3.020, 95% CI: 2.496–3.653 for elevated ALT; OR 1.689,
95% CI: 1.314–2.171 for elevated AST). Subjects with elevated liver enzymes tended to exhibit a higher
likelihood of having MetS. Even within the reference range, subjects with the highest ALT quartile
had a 1.878-times higher risk of MetS than those with the lowest ALT quartile (p < 0.001). While in the
normal AST level, we did not find a statistically significant relationship between AST level and MetS.
Table 4. Multiple logistic regression for metabolic syndrome.
Aminotransferase Levels
Normal ALT
Quartile 1
Quartile 2
Quartile 3
Quartile 4
Elevated ALT
Normal AST
Quartile 1
Quartile 2
Quartile 3
Quartile 4
Elevated AST
OR
95% CI
p-Value
1
1.113
1.375
1.878
3.020
——
1.019–1.280
1.212–1.560
1.650–2.138
2.496–3.653
<0.001 *
0.049 #
<0.001 *
<0.001 *
<0.001 *
1
0.852
0.813
0.955
1.689
——
0.756–0.959
0.713–0.926
0.844–1.080
1.314–2.171
<0.001 *
0.008 #
0.002 #
0.463
<0.001 *
Notes: Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase. Adjusted for age, sex,
race, smoking, drinking, education, physical activity, family income, history of CVD, and BMI. * p < 0.001,
# p < 0.05.
Quartile 2
Quartile 3
Quartile 4
Elevated AST
0.852
0.813
0.955
1.689
0.756–0.959
0.713–0.926
0.844–1.080
1.314–2.171
0.008 #
0.002 #
0.463
<0.001 *
Notes: Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase. Adjusted for age,
Int. J. Environ.
Res.
Public Health
2016, 13,
223
sex, race,
smoking,
drinking,
education,
physical activity, family income, history of CVD, and BMI.
* p < 0.001, # p < 0.05.
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Figure 2. Adjusted odds ratios for having MetS in four age groups, for (A) ALT and (B) AST.
Figure 2. Adjusted odds ratios for having MetS in four age groups, for (A) ALT and (B) AST.
Table 5 showed the Pearson’s correlation coefficients between the liver enzyme levels and other
Table
5 showed
theafter
Pearson’s
between
the
liver enzyme
levels
and
metabolic
variables
adjustedcorrelation
for age andcoefficients
sex. The ALT
level was
positively
correlated
with
theother
following
factors:after
BMI,adjusted
WC, SBP,for
DBP,
and
FPG;
negative
correlation
was observed
for HDL-C.
metabolic
variables
ageTG,
and
sex.
The
ALT level
was positively
correlated
with the
Similarly,
the AST
level
wasSBP,
positively
correlated
with all
the variables
listed above,
except for HDL-C
following
factors:
BMI,
WC,
DBP, TG,
and FPG;
negative
correlation
was observed
for HDL-C.
and FPG.
Similarly,
the AST level was positively correlated with all the variables listed above, except for HDL-C
and FPG.
Table 5. Correlation between serum liver enzymes and investigated variables after adjustments for
age and sex.
Table 5. Correlation between serum liver enzymes and investigated variables after adjustments for age
and sex.
ALT
AST
Variables
Pearson’s Coefficients p-Value Pearson’s Coefficients p-Value
ALT
BMI
0.178
<0.001 *
0.038 AST
<0.001 *
Variables
WC Pearson’s Coefficients
0.201
<0.001
*
0.071
<0.001
*
p-Value
Pearson’s Coefficients
p-Value
SBP
0.047
<0.001 *
0.089
<0.001 *
BMI
0.178
<0.001 *
0.038
<0.001 *
DBP
0.111
<0.001 *
0.098
<0.001 *
WC
0.201
<0.001 *
0.071
<0.001 *
TG
0.153
<0.001 *
0.09
<0.001 *
SBP
0.047
<0.001 *
0.089
<0.001 *
#
HDL-C
−0.032
0.001
0.139
0.223 *
DBP
0.111
<0.001 *
0.098
<0.001
FPG
0.055
<0.001
*
0.001
0.955
TG
0.153
<0.001 *
0.09
<0.001 *
#
Notes:
Abbreviations: ALT,
alanine aminotransferase;
aspartate aminotransferase;
BMI, body
HDL-C
´0.032
0.139
0.223mass
0.001 AST,
FPG
0.055 SBP, systolic<0.001
0.955 TG,
index;
WC, waist circumference;
blood* pressure; DBP,0.001
diastolic blood pressure;
triacylglycerol;
HDL-C,
high-density
lipoprotein cholesterol;
FPG,
fasting plasma glucose.
* p mass
< 0.001,
Notes:
Abbreviations:
ALT, alanine
aminotransferase;
AST, aspartate
aminotransferase;
BMI, body
index;
# p < 0.05.
WC, waist circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triacylglycerol; HDL-C,
high-density lipoprotein cholesterol; FPG, fasting plasma glucose. * p < 0.001, # p < 0.05.
In addition, we drew the ROC curve according to serum liver enzyme levels and prevalence of
MetS. Serum liver enzyme levels when the sum of sensitivity and specificity reached the maximum
In
addition,
we drew
theoptimal
ROC curve
according
to serum
liver
enzyme
andlevels
prevalence
value
was regarded
as the
cutoff value.
The optimal
cutoff
value
of ALTlevels
and AST
were of
MetS. Serum liver enzyme levels when the sum of sensitivity and specificity reached the maximum
value was regarded as the optimal cutoff value. The optimal cutoff value of ALT and AST levels were
20.1 U/L and 24.0 U/L, respectively. The sensitivity for diagnosis of MetS, respectively, was 76.8% for
ALT and 69.4% for AST, and the specificity, respectively, was 81.4% for ALT and 70.0% for AST.
4. Discussion
In this sample of Chinese adults, we investigated independent associations of serum ALT and
AST elevation, even within the reference range, with the prevalence of MetS. Our findings showed that
participants with higher ALT or AST level were more likely to be obese, have higher blood pressure,
TC, TG, LDL-C, FPG level, and have lower HDL-C levels. Subjects had increased prevalence of MetS
from the lowest ALT or AST quartile group to the highest quartile group.
Recent epidemiologic studies have reported associations between elevated serum levels of liver
enzymes and increased cardiovascular risk. Elevated ALT and gamma-glutamyl transferase (GGT)
have been shown to predict CVD in prospective studies [23–25]. MetS was suggested to be a risk factor
for CVD, and the prevalence had been increasing in developing countries. So the relationships between
Int. J. Environ. Res. Public Health 2016, 13, 223
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serum liver enzymes and MetS have drawn significant attention in recent years. We found that elevated
serum ALT and AST were significantly associated with increased prevalence of MetS in this Chinese
population. Regarding analysis for values above the reference, the associations between elevated ALT
or AST and prevalence of MetS had been observed in several different populations, including elderly
males [26], obese adults [27], postmenopausal women [28], and even adolescents [29]. Kim HC et al.
found that the serum ALT level was significantly related to MetS in men but not in women [30].
Previous studies also reported ALT elevation increased the risk for non-hepatic diseases including
diabetes mellitus type 2, MetS, CVD, and malignancies [31,32]. Although similar findings have already
been reported in middle-aged, urban Chinese men [33], we showed a significant association between
elevated liver enzyme levels and MetS in a large-scale general population in China. Among hepatic
enzymes, ALT is considered to be the most specific indicator of hepatic diseases and most closely
related to liver fat accumulation [34]. In our study, the positive relationship of elevated ALT with MetS
was stronger than that of elevated AST. Our data showed that subjects with elevated ALT level had
3.0-fold increased risk of MetS than partners with the lowest ALT quartile group whereas 1.7-folds in
elevated AST level. This can be explained by higher specificity of ALT to liver disease. Furthermore,
another more important finding of this study was that a statistically significant relationship was
observed between serum ALT levels within the normal range and MetS in a level-related manner.
These results were in agreement with two Japanese studies [35,36] and a Korean study [37], which
found that risk of MetS increased with elevation in serum ALT level within normal range. Previous
studies did not evaluate the association between AST levels within the reference range and MetS, but
our results indicated that no statistically significant relationship existed with prevalence of MetS and
ALT level within normal range.
The most probable explanation for our results of relationship between serum liver enzyme levels
and prevalence of MetS is NAFLD. It has been reported that, clinically, the most common etiology of
elevated ALT levels is NAFLD [10,38]. NAFLD is a probable explanation for abnormal liver enzyme
levels and a cause of asymptomatic elevation of ALT levels [39]. NAFLD is considered to be associated
with metabolic disorders, including obesity, hypertension, hyperglycemia, and dyslipidemia, which
are components of the MetS [40,41]. Therefore, this supports the notion that NAFLD is considered
a hepatic manifestation of MetS [42].
In our study, the optimal cutoff values of serum ALT and AST concentration was 20.1 U/L and
24.0 U/L, separately. The routine screening of liver enzymes and updated cutoff levels of ALT and AST
could help early detection of MetS and to arrest the progress of disease. However, more prospective
studies are needed to identify the optimal cutoff values of liver enzymes for Chinese people.
Study strengths and limitations: the strengths of this study are its population-based design, large
sample size, and the first evaluation of the associations of ALT, AST levels with MetS, both within the
normal range and elevated liver enzyme values in the general Chinese population. Several limitations
in this study need to be acknowledged. First, because of its cross-sectional design, we were unable to
determine whether or not there was a causal association. Thus, the obtained associations in this study
should be considered with caution. Second, there are known causes of elevated liver enzyme levels
that were not tested in our study, such as chronic viral hepatitis and other illnesses, and the possibility
still exists that unmeasured confounders may explain part of the association.
5. Conclusions
In summary, these representative data of the Chinese general population suggested that elevated
levels of ALT and AST, were independently associated with an increased prevalence of MetS. Moreover,
elevated ALT level was more closely associated with MetS than elevated AST levels. In addition to
that, only ALT level within reference range had significant relationship with the MetS while AST
within normal range was not associated with MetS. However, further epidemiologic investigations
using longitudinal designs are necessary to understand associations between serum ALT or AST levels
and MetS.
Int. J. Environ. Res. Public Health 2016, 13, 223
9 of 11
Acknowledgments: The authors thank Yonghong Zhang, Liying Xing and Guowei Pan for their assistance.
This study was supported by grants from the “Twelfth Five-Year” project funds (National Science and Technology
Support Program of China, Grant #2012BAJ18B02) that Yingxian Sun responsible for enable the project completion.
Author Contributions: Shuang Chen analyzed data and drafted the manuscript. Xiaofan Guo and Shasha Yu
gave guidance on writing this paper. Ying Zhou and Zhao Li performed the research. Yingxian Sun designed the
research. All authors have read and approved the final manuscript.
Conflicts of Interest: The authors declare no conflict of interest.
Abbreviations
The following abbreviations are used in this manuscript:
CNY
CVD
SBP
DBP
WC
BMI
TC
TG
HDL-C
LDL-C
FPG
ALT
AST
GGT
China Yuan
cardiovascular disease
systolic blood pressure
diastolic blood pressure
waist circumference
body mass index
total cholesterol
triacylglycerol
high-density lipoprotein cholesterol
low-density lipoprotein cholesterol
fasting plasma glucose
alanine aminotransferase
aspartate aminotransferase
gamma-glutamyl transferase
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